1. Field of the Invention
This invention relates to a method and apparatus for an in-process, automated analysis using a ratio measurement. More specifically, the disclosed In-process, Atmospheric Pressure Interface, Mass Spectrometer (IP-API-MS) apparatus and related method uses a ratio measurement to characterize the amounts or concentrations of analytes. This characterization may be optimized for quality assurance at and near instrumental detection limits.
2. Description of the Prior Art
Mass spectrometry instrumentation is frequently used as the technique of choice in measuring parts-per-billion (ppb) and sub-ppb levels of elements or compounds in aqueous and other solutions as well as in gases. Mass spectrometers are typically operated and regularly calibrated by experienced technicians. In many cases, however, unattended operation of the mass spectrometer is desired. These cases may include remote operation, around the clock monitoring, or operation either in hostile environments, or where human interaction must be minimized. One such case is that of contamination monitoring and control in the wet process baths, such as, for example, the semiconductor industry which requires a clean room environment where minimal human interaction is desired. Installation of real time, in-situ, sensors into clean room process is a major defect reduction challenge in the industry. International Technology Roadmap for semiconductors 1999 Edition: Defect Reduction, Sematech, Austin Tex., (pg. 270) (1999).
In order to accomplish unattended operation, the method should automatically monitor elemental concentrations at their threshold level, accurately and without the need to compensate for the inevitable systematic errors associated with instrument drift. Quantitation of elemental concentrations may then be obtained without the need for traditional calibration once the threshold level has been exceeded. Traditional calibration techniques use calibration standards to generate a calibration curve which relates instrument response to concentration of standards. The calibration curve is used in order to determine the concentration of unknown sample. A typical calibration curve is illustrated in FIG. 1 (curve A). Traditional techniques will not yield accurate results if the instrument response drifts or there is a response shift caused by a difference in the matrices between the standard and the sample. Mass spectrometers are especially susceptible to rapid drift causing a change in the calibration response as shown in FIG. 1 (curve B). This rapid drift results in the need for frequent recalibrations that are normally performed by experienced technicians. The effort of matching the matrices of the sample and standard must be made in order to insure ionization efficiencies, ionization suppression or enhancements remain identical between sample and standard.
Viscosity differences between the sample and standard matrices may also cause unequal instrument responses associated with changing sample introduction rates which are inevitable in real world situations. Matrix effects altering solution viscosity or ionization efficiency can result in calibration changes such as shown in FIG. 1 (curve C).
IDMS is based upon the addition of an enriched isotope standard to a sample to be analyzed. See, generally, U.S. Pat. No. 5,414,259 the disclosure of which is expressly incorporated herein by reference. After equilibration of the sample and standard, the natural isotopic ratio of the sample will have been altered by the enriched standard and the new isotopic ratio is measured by a mass spectrometer. If the concentration of an enriched isotopic standard is known, as well as the enriched isotopic ratio, then the measured ratio of altered natural elemental isotopes provides the elemental concentration of the sample. This method has only a very few well-defined possibilities for error. Each of these possibilities can be calibrated and eliminated, leaving the uncertainty in ratio determination of the two isotopes as the final error for the measurement. This uncertainty is based on the mass spectrometer's ability to make this isotopic ratio measurement. If the enriched isotope standard of known concentration is introduced, in a precisely controlled fashion, to the sample on-line, all normal interferences are eliminated for each element or species being measured. As only the altered isotope ratio is needed to obtain the concentration of the sample, the physical and chemical differences of flow rate and ionization efficiencies are essentially eliminated. Therefore, IDMS is an ultimate correction technique for both long-term and short-term instrument drift, as well as countering non-spectroscopic interference. This procedure, in general, provides accurate detection for the instrument and process necessary for quality control in ultra-trace analysis. In addition, traditional IDMS has been employed primarily with both Inductively Coupled Plasma Mass Spectrometers (ICP-MS) and Thermal Ionization Mass Spectrometers (TIMS). Both ICP-MS and TIMS instrumentation are not deemed suitable for operation in an unattended mode. Fassett, J. D., Paulsen, P. J. Isotope-dilution mass spectrometry for accurate elemental analysis, Anal. Chem. (1989) 61 643A-649A; Rottmann, L., Heumann, K. G., Development of an on-line Isotope Dilution Technique with HPLC/ICP-MS for the accurate determination of elemental species. Fresenius J. Anal. Chem., (1994) 350 221-227; Rottmann, L., Heumann, K. G., Determination of Heavy Metal Interactions with Dissolved Organic Materials in Natural Aquatic Systems by Coupling High-Performance Liquid Chromatography System with an Inductively Coupled Plasma Mass Spectrometer. Anal. Chem., (1994) 66, 3709-3715; Heumann, K. G., Rottmann, L., Vogl, J., Elemental Speciation with Liquid Chromatography-Inductively Coupled Plasma Isotope Dilution Mass Spectrometry. J. Anal. Atom. Spectro. (1994) 9 1351-1355; Horn, M., Heumann, K. G., Comparison of Heavy Metal Analysis in Hydrofluoric Acid used in Microelectronic Industry by ICP-MS and Thermal Ionization Isotope Dilution Mass Spectrometry, Fresenius J. Anal. Chem., (1994) 350 286-292.
A method of using on-line IDMS as an internal standard with an ICP-MS instrument has been suggested with an enriched isotopic standard being continuously introduced into the sample stream and mixed (allowed to equilibrate) prior to introduction into an ICP-MS instrument. Rottmann, L., Heumann, K. G., Development of an on-line Isotope Dilution Technique with HPLC/ICP-MS for the accurate determination of elemental species. Fresenius J. Anal. Chem., (1994) 350 221-227; Rottmann, L., Heumann, K. G., Determination of Heavy Metal Interactions with Dissolved Organic Materials in Natural Aquatic Systems by Coupling High-Performance Liquid Chromatography System with an Inductively Coupled Plasma Mass Spectrometer. Anal. Chem., (1994) 66, 3709-3715; Heumann, K. G., Rottmann, L., Vogl, J., Elemental Speciation with Liquid Chromatography-Inductively Coupled Plasma Isotope Dilution Mass Spectrometry. J. Anal. Atom. Spectro. (1994) 9 1351-1355. An on-line HPLC/ICP-IDMS method for elemental speciation was tested. In the case published, heavy metals in humic complexes found in natural waters were measured using a High Resolution ICP-MS with either an iron, copper, or a molybdenum enriched spike introduced as the IDMS calibration standard. Selection of which element standard was contingent upon the element to be analyzed in the sample. Rottmann, L., Heumann, K. G., Development of an on-line Isotope Dilution Technique with HPLC/ICP-MS for the accurate determination of elemental species. Fresenius J. Anal. Chem., (1994) 350 221-227; Rottmann, L., Heumann, K. G., Determination of Heavy Metal Interactions with Dissolved Organic Materials in Natural Aquatic Systems by Coupling High-Performance Liquid Chromatography System with an Inductively Coupled Plasma Mass Spectrometer. Anal. Chem., (1994) 66, 3709-3715; Heumann, K. G., Rottmann, L., Vogl, J., Elemental Speciation with Liquid Chromatography-Inductively Coupled Plasma Isotope Dilution Mass Spectrometry. J. Anal. Atom. Spectro. (1994) 9 1351-1355. It was stated that “quantitative chromatographic separation of the species to be analyzed” is one of the preconditions for this method and “quantitative separation is essential before the spiking step takes place (for a species-unspecific spike).” It was also stated that “(for a species-unspecific spike), equilibration between the separated species and spike must be guaranteed . . . by high temperature of the argon plasma (in ICP-MS).” Rottmann, L., Heumann, K. G., Development of an on-line Isotope Dilution Technique with HPLC/ICP-MS for the accurate determination of elemental species. Fresenius J. Anal. Chem., (1994) 350 221-227. HPLC separation and ICP-MS measurement are two essential parts of their method.
Semiconductor manufacturers rely on the purity of chemicals to create sub-micron devices from silicon wafers. Impure chemicals tend to result in devices that will not work. It is, therefore, important to know whether a wet chemical is, in fact, pure, or adequately pure. Current methods of determining purity tend to be expensive, slow, off-line chemical analyzers. This problem becomes enhanced with continued device shrinkage as in the move to 300-mm wafers and copper interconnects. Captive and contract analytical laboratories tend to produce chemical assays and time frames ranging from 24 to 72 hours. One of the consequences of this lack of timely information is the failure to know when to dispose of these expensive chemicals.
It has been suggested to employ in-line ICP-MS in a method of monitoring concentration of metals in silicon wafer cleaning baths. See Using ICP-MS for in-line monitoring of metallics in silicon wafer cleaning baths.
Isotope dilution Mass Spectrometry for ultra-trace analysis has been previously known. Fassett, J. D. and Kingston, H. M., Determination of Nanogram Quantities of Vanadium in Biological Material by Isotope Dilution Thermal Ionization Mass Spectrometry With Ion Counting Detection, Anal. Chem., (1985) 57 2474-2478. In this publication ultra-trace analysis uses IDMS in the traditional way with isotopically enriched spikes in batch spiked standards. These isotopes are spiked into low concentration samples and blanks and any species information is removed using the batch sample method. Complete transformation of all species is traditionally a prerequisite to most IDMS protocols to prevent multiple species existing in the sample simultaneously. In addition, this transformation prevents the spiked isotopes and the sample isotopes from existing in different species form. As a result, elemental species determinations and evaluations providing both are not possible and are in fact prevented by the traditional IDMS technique.
U.S. Pat. No. 5,012,052 discloses a patent by Hayes describes a method for isotope monitoring for gas that is an on-line continuous combustion from organic components to assist in the determination of the origin of objects based on the C-12 and C-14 ratios. This method requires a combination of gas chromatograph and flame ionization detector (FID), and palladium separator and oxygen charged combustion reactor prior to mass spectrometry. The method requires the use of the combustion chamber, and a palladium separator prior to the mass spectrometer. The goal of this method and instrument is comparison with an isotopic standard to establish isotopic ratios for carbon for origin identification of gases specifically using C-12 and C-14. There is no attempt to perform trace analysis of transition or other metals and quantification is not based on isotope dilution measurements. This method will not work for metals.
U.S. Pat. No. 5,572,024 discloses method and apparatus for quieting the introduction into a mass spectrometer from inductively coupled plasma (ICP) devise by manipulating skimmer cone diameters and pressure. The invention is an improvement of ratio precision measurements over well known ICP-MS and MIP-MS (microwave induced plasma) technology. It describes modifications to a mass spectrometer inlet that enables more precise measurement of isotopes. It requires a plasma device and also reduces the sensitivity of the mass spectrometer.
U.S. Pat. No. 5,872,357 discloses a series of calibrant compositions for organic compounds that enable calibration across a broad mass spectral range for electrospray mass spectrometry, as well a method of using these organic calibrant compositions to calibrate a mass spectrometer. The invention provides a class of new organically based calibrant compositions and limits its application to the usage of these calibrant compositions.
U.S. Pat. No. 6,032,513 discloses a hollow electrode for the improvement of ionization in an atmospheric-pressure ionization source and substitute a more easily ionized carrier gas for the sample gas stream. The disclosure is specific for gas analysis and requires the substitution of the gas stream and the use of a hollow electrode prior to a mass spectrometric measurement. This technology is not applicable in the isotopically based measurements that are the focus of the present invention.
IDMS using Flow Injection Analysis (FIA) introduction to an ICP-MS has been known. Viezian, Miklos; Alexandra Lasztity, Zioaru Wang and Ramon M. Barnes, On-Line Isotope Dilution and Sample Dilution by Flow Injection and Inductively Coupled Plasma Mass Spectrometry, J. Anal. Atom. Spectro., (1990) 5 125-133. This technique uses FIA to mix the isotopically enriched spike and the sample prior to introduction to the ICP-MS. The spike and sample are injected simultaneously to form a zone within a neutral carrier liquid prior to introduction to the ICP-MS. The volume of a fixed sample loop controls the amounts of spike and sample. Physical mixing of the two solutions occurs between the confluence point and the nebulizer. As in traditional IDMS methods species information is unavailable, as the enriched spike is species-unspecific. In addition, the technique suggested on-line dilution using an inert reagent; a technique that is easily accomplished using FIA.
An automated calibrant apparatus was disclosed in U.S. Pat. No. 5,703,360. It introduces a standard reference solution automatically into a mass spectrometer ESI or Atmospheric Pressure Chemical Ionization (APCI) to calibrate or tune the mass spectrometer. In this patent a switching valve is used to introduce the standard as desired to the ESI or APCI. As the standard reference solution and the sample solution are from different sources matrix effects are not eliminated.
U.S. Pat. No. 5,703,360 discloses that one or two traditional standard reference solutions can be used to tune the mass spectrometer with respect to the mass axis, and to assess the functionality of the instrument and to re-calibration the instrument. This technique of introducing two sequential calibration standards will not eliminate the short or long-term drift that can be a problem in unattended operation of a mass spectrometers. See U.S. Pat. No. 5,703,360.
Atmosphere pressure ionization (API) techniques includes electrospray (ES) ionization and atmosphere pressure chemical ionization (APCI). This technique has been widely used to characterize bio-molecules such as peptides, proteins, nucleic acids and carbohydrates. Cole, R. B. Electrospray Ionization Mass Spectrometry: Fundamentals Instrumentation & Applications; John Wiley & Sons, Inc.: New York, 1997. It is also used to qualitatively determine the presence of inorganic, organometallic and complexed metal ions, but quantifying that information has remained a significant challenge. High background due to chemical noise and signal suppression (matrix effects) appear to be the uppermost limiting factors for the quantification of most analytes. Stewart, I. I., Electrospray Mass Spectrometry: a Tool for Elemental Speciation, Spectrochim. Acta. Part-B. (1999) 54B 1649-1695. Collision-induced dissociation (CID) generates energetic collisions and can simplify mass spectra, reduce the background and increase the sensitivity. However, stable operation is limited to a narrow range of solution conductivities and can cause inherent non-linearity signal response during the quantification.
Speciated Isotope Dilution Mass Spectrometry (SIDMS) has been developed to assess the quantification of species and also their transformations. See U.S. Pat. No. 5,414,259. In SIDMS a predetermined species is specifically isotopically labeled and introduced to accomplish these measurements. The species of interest is previously known and specifically evaluated.
In summary, a method and associated apparatus have been developed to accomplish unattended operation of an apparatus that will automatically and accurately monitor elemental concentration threshold levels, identify, and quantify elemental contaminants or compounds and species in fluids.